The FDA accepted the supplemental biologics license application (sBLA) for emapalumab-Izsg (Gamifant; Sobi, Inc.) to treat both adult and pediatric patients with hemophagocytic lymphohistiocytosis (HLH)/macrophage activation syndrome (MAS) in Still disease with an inadequate response or intolerance to glucocorticoids, or with recurrent MAS. The application, which was based on pooled data from 2 studies, was granted priority review with a Prescription Drug User Fee Act of June 27, 2025.1,2
Emapalumab is an anti-interferon gamma (IFN-γ) monoclonal antibody that binds and neutralizes interferon gamma (IFN-y) that was initially approved by the FDA in 2018 for the treatment of adult and pediatric (newborn and older) patients with primary HLH with refractory, recurrent, or progressive disease or intolerance with conventional HLH therapy. It is the first and only treatment approved by the FDA for this indication.1
HLH/MAS, which is a form of HLH, is a severe complication of rheumatic diseases that most frequently occurs in Still disease, including systemic juvenile idiopathic arthritis and adult-onset Still disease. HLH/MAS is a rare systemic disorder of hyperinflammation with common clinical manifestations such as high persistent fever, elevated ferritin, cytopenias, coagulopathies, and hepatosplenomegaly.1
About the Trials
EMERALD (NI-0501-14)
- Trial Name: Evaluate Efficacy, Safety and Tolerability, PK and PD of Emapalumab in Children and Adults With MAS in Still's or SLE (EMERALD)
- ClinicalTrials.gov ID: NCT05001737
- Sponsor: Swedish Orphan Biovitrum
- Completion Date (Estimated): September 2025
NI-0501-06
- Trial Name: A Study to Investigate the Safety and Efficacy of Emapalumab, an Anti-IFN-gamma mAb in Patients With Systemic Juvenile Idiopathic Arthritis (sJIA) or Adult-onset Still's Disease (AOSD) Developing Macrophage Activation Syndrome/Secondary HLH (MAS/sHLH)
- ClinicalTrials.gov ID: NCT03311854
- Sponsor: Swedish Orphan Biovitrum
- Completion Date: May 19, 2020
The sBLA acceptance and priority review come after positive data from 2 open-label, single-arm, interventional phase 3 studies—EMERALD (also called NI-0501-14; NCT05001737)3 and NI-0501-06 (NCT03311854)4—which enrolled a total of 39 patients with MAS. In these trials, patients received intravenous infusions of emapalumab, and in NI-0501-06, patients were given an initial dose of 6 mg/kg before continuing treatment with 3-mg/kg doses every 3 days until day 15, then twice per week for 2 weeks (until day 28).1,3,4
Key results—which were presented on November 19 at the 2024 American College of Rheumatology Convergence in Washington, DC—demonstrated that at week 8, approximately 53.8% (n = 21) of patients across both studies achieved a complete response (95% CI: 37.2%–69.9%) while receiving treatment with emapalumab. At any time during the studies’ durations, 33 patients (85%) achieved a complete response. Additionally, the weekly mean glucocorticoid doses were reduced by about 70.1% following 2 weeks of treatment, and by week 8, glucocorticoids were tapered to a clinically meaningful dose of 1 mg/kg/day or less in 28 patients (72%) and to 0.5 mg/kg/day or less in 17 patients (44%).2
Further, 32 patients (82.4%) achieved an overall response (OR) by week 8, and this was observed as early as day 5 (median time to first OR: 2.3 weeks). Clinical MAS remission was achieved by 32 patients (82.1%), with a median time to clinical remission of about 3.3 weeks. About 94.9% (n = 34) patients were alive at week 8. There were no new safety concerns identified in either of the studies.2
"HLH/MAS in Still disease is a serious and potentially fatal complication where patients can experience intense hyperinflammation and even multiple organ failure," Lydia Abad-Franch, MD, MBA, head of research and development, chief medical officer at Sobi, said in a news release. "There is no approved therapy for HLH/MAS today. Emapalumab selectively neutralizes IFN-γ, a key driver of hyperinflammation, and if approved, may also help reduce the need for high-dose glucocorticoids in these patients."1
REFERENCES
3. Evaluate Efficacy, Safety and Tolerability, PK and PD of Emapalumab in Children and Adults With MAS in Still's or SLE (EMERALD). ClinicalTrials.gov identifier: NCT05001737. Updated October 15, 2024. Accessed February 27, 2025. https://clinicaltrials.gov/study/NCT05001737
4. A Study to Investigate the Safety and Efficacy of Emapalumab, an Anti-IFN-gamma mAb in Patients With Systemic Juvenile Idiopathic Arthritis (sJIA) or Adult-onset Still's Disease (AOSD) Developing Macrophage Activation Syndrome/Secondary HLH (MAS/sHLH). ClinicalTrials.gov identifier: NCT03311854. Updated May 17, 2022. Accessed February 27, 2025. https://www.clinicaltrials.gov/study/NCT03311854
